Research: Much of our adult behavior reflects the neural circuits sculpted by experience in infancy and early childhood. At no other time in life does the surrounding environment so potently shape brain function – from basic motor skills, sensation or sleep to higher cognitive processes like language. Understanding how this plasticity waxes and wanes with age carries an impact far beyond neuroscience, including education policy, therapeutic approaches to developmental disorders or strategies for recovery from brain injury in adulthood. Our laboratory explores the mechanisms underlying critical periods of brain development. Research is aimed at the interface between cell biology and neuroscience - applying cellular/molecular techniques to elucidate complex neural systems. We have achieved the first direct control over critical period timing in the visual system (Hensch 2005). By manipulating inhibitory transmission in the neocortex, amblyopic effects of deprivation are delayed (by gene-targeted reduction of GABA synthesis) or accelerated (by cortical infusion of a positive GABA receptor modulator, diazepam). A major goal now is to establish the generality of this principle of excitatory-inhibitory balance across brain regions and systems. Remarkably, a specific, local inhibitory circuit may drive critical period onset in visual cortex. Downstream of this trigger lies an extracellular proteolytic cascade and structural reorganizations, which ultimately consolidate plasticity. Imaging efforts at the Center for Brain Science will visualize the dynamic re-wiring of connections in mouse models to provide further insight for translational research into disorders of critical period development at Children’s Hospital Boston.
Selected Publications: Hensch, T.K. (2005) Critical period plasticity in local cortical circuits. Nat. Rev. Neurosci. 6: 877-888. Mataga, N., Mizuguchi, Y. & Hensch, T.K. (2004) Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator. Neuron 44: 1031-1041. Fagiolini, M., Fritschy, J-M., Löw, K., Möhler, H., Rudolph, U. & Hensch, T.K. (2004) Specific GABAA circuits for visual cortical plasticity. Science 303: 1681-1683. Hensch, T.K. (2004) Critical Period Regulation. Annu. Rev. Neurosci. 27: 549-579. Miyamoto, H., Katagiri, H. & Hensch, T.K. (2003) Experience-dependent slow-wave sleep development. Nature Neurosci. 6: 553-554.
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